Adenosine monophosphate deaminase -AMP-, deficiency ..., myoadenylate deaminase deficiency (Adenosine monophosphate deaminase deficiency) - Gen AMPD1

Deficiency monophosphate adenosine deaminase (DMPA) is the most common muscle metabolic disease, affecting 1 to 2% of the European population. Affected individuals do not encode sufficient quantities of the enzyme AMP deaminase (AMPD). In most people, AMP deaminase deficiency does not cause any symptoms.

People who develop symptoms usually have fatigue, myalgia, or cramps after exercise or prolonged physical activity (exercise intolerance). After strenuous activity, affected individuals become tired more quickly and remain tired longer than usual. In rare cases, affected individuals appear more pronounced symptoms include severe muscle weakness, hypotonia and atrophy, although it is unclear if these symptoms are due solely to AMP deaminase deficiency or additional conditions. Exercise intolerance associated with AMP deaminase deficiency is evident usually in childhood or early adulthood.

This process is due to mutations in the gene AMPD1 (adenosine monophosphate deaminase 1), located on the short arm of chromosome 1 (1p13.2). This gene encodes the AMP deaminase (adenosine monophosphate deaminase) enzyme found in skeletal muscle, which is involved in energy production in muscle cells. Specifically involved in the cycle of purine nucleotides catalyzing the deamination of adenosine monophosphate (AMP) in inosine monophosphate (IMP), releasing a molecule of ammonium (NH 4 +). In cases where the muscles demand require higher than usual energy, for example during physical exercise, two molecules of ADP (adenosine diphosphate) become a molecule of ATP (adenosine triphosphate) and other MPA. Thus, there is more energy in the form of ATP.

They have been identified at least 9 mutations in the gene AMPD1, of which 7 are missense mutations and 2 are small deletions. Mutations of this gene alter the function of the enzyme, affecting the ability of the muscle cells for energy. In most cases a mutation is found in exon 2 (Q12X: Gly12Ter, C34T), which leads to an early stop signal in encoding the enzyme. Other mutations involved were as follows: in exon 3 (P48L: Pro48Leu, C143T -polimorfismo activity compared with normal [wild] gene -; Asp15Gly, A44G); in exon 5 (Gln156His, G468T); in exon 7 (K287I: Lys287Ile, A860T); in exon 8 (Met310Ile, G930T); in exon 9 (Arg388Trp, C1162T) in exon 10 (Arg425His, G1274A), or a deletion of intron 2 (IVS2- [4-7] delCTTT). AMP molecules in individuals deficient DMPA can not cleavable IMP and ammonia, accumulate in the blood AMP. The cycle of purine nucleotides also produces fumarate, an intermediate of the Krebs cycle, so AMPD deficiency affects an essential element, fumarate, muscle energy metabolism, causing myalgia and other muscle problems. Other people with mutations in this gene do not show any signs or symptoms associated with AMP deaminase deficiency. It is believed that these individuals other factors, both genetic and environmental, can determine whether a person develops signs and symptoms of the disease.

This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.


Tests performed in IVAMI: in IVAMI perform detection of mutations associated with adenosine deaminase deficiency monophosphate (AMP), by complete PCR amplification of the exons of the gene AMPD1,   and subsequent sequencing. We recommend starting the study to detect the most common in exon 2 (Q12X) mutation, and if not present, perform the complete sequencing of the remaining exons.


Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated card blood sample   desiccated (IVAMI can mail the card to deposit the blood sample).